Rethinking Hydrolytic Imidazoline Ring Expansion: A Common Approach to the Preparation of Medium-Sized Rings via Side-Chain Insertion into [1.4]Oxa- and [1.4]Thiazepinone Scaffolds

Elena Reutskaya, Angelina Osipyan, Alexander Sapegin, Alexander S. Noyikov, Mikhail Krasavin*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

The previously reported ring-expansion strategy involving hydrolytically prone imidazoline rings was thought to include the formation of a hydrated imidazoline intermediate. In this work, we accessed the latter via the addition of a 2-aminoethyl side chain onto a lactam moiety. This led to an efficient three-atom ring expansion of diarene-fused [1.4]oxazepines and [1.4]thiazepines and led us to propose to term this common approach the hydrated imidazoline ring expansion (HIRE) reaction. The strategy was extended to the insertion of longer (containing up to five atoms) side chains, and thus, larger (11- to 12-membered) diarene-fused rings were obtained via the homo-HIRE and homo(2)-HIRE reactions, respectively. This underscores the utility of the HIRE reaction for the preparation of medium-sized rings, an important class of chemical tools for interrogation of various biological targets.

Original languageEnglish
Pages (from-to)1693-1705
Number of pages13
JournalJournal of Organic Chemistry
Volume84
Issue number4
DOIs
Publication statusPublished - 15-Feb-2019
Externally publishedYes

Keywords

  • TRANSAMIDATION REACTIONS
  • BETA-LACTAMS
  • THERMOCHEMISTRY
  • MACROCYCLES

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